Publications by authors named "Danny Liew"

369 Publications

Dihydrosphingosine driven enrichment of sphingolipids attenuates TGFβ induced collagen synthesis in cardiac fibroblasts.

Int J Cardiol Heart Vasc 2021 Aug 6;35:100837. Epub 2021 Jul 6.

Biomarker Discovery Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia.

The sphingolipid de novo synthesis pathway, encompassing the sphingolipids, the enzymes and the cell membrane receptors, are being investigated for their role in diseases and as potential therapeutic targets. The intermediate sphingolipids such as dihydrosphingosine (dhSph) and sphingosine (Sph) have not been investigated due to them being thought of as precursors to other more active lipids such as ceramide (Cer) and sphingosine 1 phosphate (S1P). Here we investigated their effects in terms of collagen synthesis in primary rat neonatal cardiac fibroblasts (NCFs). Our results in NCFs showed that both dhSph and Sph did not induce collagen synthesis, whilst dhSph reduced collagen synthesis induced by transforming growth factor β (TGFβ). The mechanisms of these inhibitory effects were associated with the increased activation of the de novo synthesis pathway that led to increased dihydrosphingosine 1 phosphate (dhS1P). Subsequently, through a negative feedback mechanism that may involve substrate-enzyme receptor interactions, S1P receptor 1 expression (S1PR1) was reduced.
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http://dx.doi.org/10.1016/j.ijcha.2021.100837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264607PMC
August 2021

Reassessing the cost-effectiveness of Nivolumab for the treatment of renal cell carcinoma based on mature survival data, updated safety and lower comparator price.

J Med Econ 2021 Jul 14. Epub 2021 Jul 14.

Monash University, Melbourne, Australia.

Aims: The aim of this study was to estimate the cost-effectiveness of nivolumab versus everolimus for 2-line treatment of renal cell carcinoma (RCC) based on mature data, updated safety and decreased everolimus price.

Materials And Methods: A 3-state (pre-progression/progression free disease, progressive disease and death) Markov model was developed from the perspective of the Australian health care system. Two scenarios were tested. Scenario 1 used 30-months clinical data and scenario 2 used updated 80-months clinical data with updated everolimus price. Inputs for quality-of-life and costs were informed by the literature and government sources. Incremental cost effectiveness ratio (ICER) per quality adjusted life years (QALY) gained was reported and an ICER threshold of AU$75,000 was assumed. Threshold analysis was performed, and uncertainty was explored using one-way and probabilistic sensitivity analyses.

Results: In scenario 1, the model estimated 1.73 QALYs at a cost of AU$105,000 for nivolumab and 1.48 QALYs at AU$38,000 for everolimus with an ICER = AU$266,871/QALY gained. A rebate of 54.4% was needed for nivolumab to reach the ICER threshold. For scenario 2, 1.93 QALYs at AU$111,418 was estimated for nivolumab and 1.60 QALYs at AU$31,942 for everolimus with an ICER of AU$213,320/QALY gained. The rebate needed to reach the ICER threshold was 54.9%. One-way sensitivity analyses for both scenarios showed that the cost of nivolumab, time horizon and utilities were main drivers. The cost-effectiveness acceptability curves highlighted the differences in cost-effectiveness of the 2 scenarios, as well as significant uncertainty in the results.

Conclusions: A 54% rebate of the published price is needed for nivolumab to be cost-effective in Australia for the treatment of RCC. At that rebate, nivolumab remains cost-effective despite severe price erosion of everolimus because of improved longer term follow-up data. We recommend that generic price erosion should be accounted for when performing cost-effectiveness analysis.
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http://dx.doi.org/10.1080/13696998.2021.1955540DOI Listing
July 2021

Sex differences in Cardiac electronic device implantation: Outcomes from an Australian multi-centre clinical quality registry.

Int J Cardiol Heart Vasc 2021 Aug 23;35:100828. Epub 2021 Jun 23.

Warringal Private Hospital, Melbourne, Australia.

Background: There is uncertainty regarding whether outcomes after Cardiac Implantable Electronic Devices (CIED) differ between women and men. There are no prospectively collected data regarding Australian CIED outcomes. This study aimed to determine whether the characteristics and outcomes of Australian patients undergoing CIED implantation differ by sex.

Methods: We prospectively followed 5,360 patients undergoing CIED implantation between 2015 and 2019 in a large multi-centre Australian registry. Patient characteristics, procedural data, medications and clinical outcomes to 1 year were analysed.

Results: The mean age was 76.2 + 11.2 years, and 2022 (37.7%) were female. Women were older than men at device implantation (77.0 ± 11.6 years vs. 75.5 ± 10.9 years, p < 0.001). Most implants were de novo (79.7%). Pacing was more commonly for sick sinus syndrome in women than men (54.4% vs. 47.2%, p < 0.001) and less often for A-V block (28.3% vs. 35.1%, p < 0.001). Adverse events at 30 days were low compared to international cohorts, for mortality (0.06%) and major complications (0.6%). There were no significant sex differences (women vs. men) for death (HR 1.33, 95% CI 0.58-3.13, p = 0.49) or major complications (HR 1.41, 95% 95% CI 0.65-3.03, p = 0.39). At 1-year, there was no difference in major complications or risk-adjusted all-cause mortality (HR 1.05, 95% CI 0.70-1.29, p = 0.77) between women and men.

Conclusions: Clinical practice and 30-day outcomes after CIED implantation in Australia are consistent with international reports. There were no differences in procedural complication rates or clinical outcomes at 1-year between women and men, regardless of age or CIED system implanted.
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http://dx.doi.org/10.1016/j.ijcha.2021.100828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246382PMC
August 2021

Endoscopic Prediction of Crohn's Disease Postoperative Recurrence.

Inflamm Bowel Dis 2021 Jul 7. Epub 2021 Jul 7.

Department of Gastroenterology, St. Vincent's Hospital and Department of Medicine, The University of Melbourne, Melbourne, Australia.

Background: The presence and severity of endoscopic recurrence after Crohn's disease intestinal resection predicts subsequent disease course. The Rutgeerts postoperative endoscopic recurrence score is unvalidated but has proven prognostically useful in many clinical studies. This study aimed to investigate the association between specific early endoscopic findings and subsequent disease course.

Methods: In the setting of a randomized controlled trial (the POCER study), 85 patients underwent colonoscopy at 6 and 18 months after intestinal resection. Patients received 3 months of metronidazole, and high-risk patients received a thiopurine (or adalimumab if they were thiopurine intolerant). For endoscopic recurrence (Rutgeerts score ≥i2) at 6 months, patients stepped up to a thiopurine, fortnightly adalimumab with thiopurine, or weekly adalimumab. Central readers confirmed Rutgeerts, Simple Endoscopic Score for Crohn's Disease, Crohn's Disease Endoscopic Index of Severity scores, and 5 newly tested endoscopic parameters: anastomotic ulcer depth (superficial vs deep), number of ulcers (0, ≤2, >2), ulcer size (1-5 mm, ≥6 mm), circumferential extent of ulceration (<25%, ≥25%), and the presence or absence of stenosis. The POCER index, based on the 6-month postoperative findings, was then developed in relation to predicting the endoscopic outcome at 18 months.

Results: Of the 5 parameters, the combination of ulcer depth and circumference at the anastomosis at 6 months was associated with endoscopic recurrence at 18 months (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.03-2.50; P = 0.035) with an area under the receiver operating characteristic curve of 0.62 (95% CI, 0.5-0.75). The combination of these 2 parameters formed the basis of the POCER index (range, 0-4 with 0 denoting no ulcers and 4 denoting deep ulceration with >25% circumferential involvement). The new index had a strong correlation with the Rutgeerts score measured at the same time points: Spearmans' r = .80 at 6 months and r = .77 at 18 months (P < 0.001 at both time points). A POCER index of ≥2 and a Rutgeerts score of ≥i2 both had a sensitivity of 0.41 for recurrence; however, the POCER index had a higher specificity (0.8 and 0.67, respectively). The POCER index at 6 months was associated with endoscopic recurrence at 18 months (OR, 1.5; 95% CI, 1.2-2.0; P = 0.002; area under the receiver operating characteristic curve of 0.70; 95% CI, 0.57-0.82), but the Rutgeerts score was not (OR, 1.2; 95% CI, 0.8-1.8; P = 0.402).

Conclusions: The POCER postoperative index comprises 2 key endoscopic factors related to the anastomosis that are associated with subsequent disease progression. A higher score, comprising the adverse prognostic factors of deep or circumferentially extensive anastomotic ulceration, may help identify patients who require more intensive therapy.
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http://dx.doi.org/10.1093/ibd/izab134DOI Listing
July 2021

Potential positive effects of bariatric surgery on healthcare resource utilisation.

ANZ J Surg 2021 Jul 5. Epub 2021 Jul 5.

Department of Surgery, Monash University Central Clinical School, Alfred Health, Melbourne, Victoria, Australia.

Background: To determine whether a bariatric surgical procedure is associated with a reduction in healthcare utilisation among patients with obesity and high pre-procedural healthcare needs.

Methods: Design: Retrospective cohort study.

Setting: Tertiary Victorian public hospital.

Participants: Twenty-nine adults who underwent publicly funded primary bariatric surgery between 2008 and 2018 at the Alfred Hospital, Melbourne and had high resource use over the year prior to surgery, defined as at least two of ≥3 hospital admissions, ≥7 inpatient bed days for obesity-related co-morbidities or inpatient hospital costs ≥$10 000.

Main Outcome Measures: Change in inpatient and outpatient resource use.

Results: After 1 year following bariatric surgery, total hospital bed days decreased from 663 to 80 and the median (Q1, Q3) per patient decreased from 7 (4.5, 15) to 5 (2.25, 9.75) (p = 0.001) and the total number of hospital admissions fell from 118 to 67 (p < 0.001). The median cost of inpatient care decreased from $11 405 ($4408, $22251) to $3974 ($0, $4325) per annum (p < 0.001). The total and median number of outpatient attendances did not significantly change 12 months after bariatric surgery, but the demand for outpatient services unrelated to bariatric surgery declined by a median of four visits per patient (p = 0.013).

Conclusions: The evidence from this small pilot study suggests that Bariatric surgery has the potential to decrease resource use and inpatient hospital costs over a 1-year time frame for obese patients with high resource use. These data will be used to design a prospective randomised controlled trial to provide more definitive information on this important issue.
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http://dx.doi.org/10.1111/ans.17049DOI Listing
July 2021

Prospective randomised controlled trial of adults with perianal fistulising Crohn's disease and optimised therapeutic infliximab levels: PROACTIVE trial study protocol.

BMJ Open 2021 Jul 1;11(7):e043921. Epub 2021 Jul 1.

South Western Sydney Clinical School, University of New South Wales, Sydney, New South Wales, Australia

Introduction: Perianal fistulising Crohn's disease (pfCD) can be somewhat treatment refractory. Higher infliximab trough levels (TLIs) may improve fistula healing rates; however, it remains unclear whether escalating infliximab therapy to meet higher TLI targets using proactive, or routine, therapeutic drug monitoring (TDM) improves outcomes. This randomised controlled trial aimed to assess whether infliximab therapy targeting higher TLIs guided by proactive TDM improves outcomes compared with standard therapy.

Methods And Analysis: Patients with active pfCD will be randomised 1:1 to either the proactive TDM arm or standard dosing arm and followed up for 54 weeks. Patients in the proactive TDM arm will have infliximab dosing optimised to target higher TLIs. The targets will be TLI ≥ 25 µg/mL at week 2, ≥ 20 µg/mL at week 6 and ≥ 10 µg/mL during maintenance therapy. The primary objective will be fistula healing at week 32. Secondary objectives will include fistula healing, fistula closure, radiological fistula healing, patient-reported outcomes and economic costs up to 54 weeks. Patients in the standard dosing arm will receive conventional infliximab dosing not guided by TLIs (5 mg/kg at weeks 0, 2 and 6, and 5 mg/kg 8 weekly thereafter). Patients aged 18-80 years with pfCD with single or multiple externally draining complex perianal fistulas who are relatively naïve to infliximab treatment will be included. Patients with diverting ileostomies or colostomies and pregnant or breast feeding will be excluded. Fifty-eight patients per arm will be required to detect a 25% difference in the primary outcome measure, with 138 patients needed to account for an estimated 6.1% primary non-response rate and 10% dropout rate.

Ethics And Dissemination: Results will be presented in peer-reviewed journals and international conferences. Ethics approval has been granted by the South Western Sydney Local Health District Human Research Ethics Committee in Australia.

Trial Registration Number: Australian New Zealand Clinical Trials Registry (ACTRN12621000023853); Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2020-043921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252869PMC
July 2021

The Health and Productivity Burden of Depression in South Korea.

Appl Health Econ Health Policy 2021 Jun 25. Epub 2021 Jun 25.

School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.

Objectives: Major depression in South Korea, which remains under-diagnosed and under-treated, increases the risk of premature death, and reduces quality of life and work productivity. The aim of this study was to quantify the depression-related health and productivity loss in South Korea in terms of life-years lost and productivity-adjusted life-years (PALYs) lost.

Method: Age and sex-specific life table models simulated follow-up of South Koreans with depression aged 15 to 54 years, until 55 years. Depression was defined as major depression. Inputs were drawn from national datasets and published sources. Models were constructed for the cohort with depression and repeated assuming they had no depression. Differences in total deaths, years of life, and PALYs represented the impact of depression. PALYs were ascribed a financial value equivalent to total gross domestic product (GDP) divided by the number of equivalent full-time workers (KRW81,507,146 or USD74,748). All outcomes were discounted by 3% per annum.

Results: In 2019, there were more than 500,000 people aged 15-54 years with major depression in South Korea. We predicted that until this cohort reached age 55 years, and assuming 22.2% of people with depression are treated, depression led to 12,000 excess deaths, more than 55,000 discounted years of life lost and 1.6 million discounted PALYs lost, equating to KRW133 trillion (USD122 billion) in lost GDP. Applying treatment-related response and remission rates of 11.8% and 42.1%, respectively, and a non-response/non-remission rate of 46.1%, increased the total number of PALYs lost by almost 6.0%.

Conclusions: Our study highlights the considerable productivity loss attributable to depression among South Koreans over their working lifetime. Better prevention and treatment of depression is needed for long-term economic gains.
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http://dx.doi.org/10.1007/s40258-021-00649-1DOI Listing
June 2021

Cost Burden and Cost-Effective Analysis of the Nationwide Implementation of the Quality in Acute Stroke Care Protocol in Australia.

J Stroke Cerebrovasc Dis 2021 Aug 19;30(8):105931. Epub 2021 Jun 19.

School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. Electronic address:

Objectives: The Quality in Acute Stroke Care (QASC) protocol is a multidisciplinary approach to implement evidence-based treatment after acute stroke that reduces death and disability. This study sought to evaluate the cost-effectiveness of implementing the QASC protocol across Australia, from a healthcare and a societal perspective.

Materials And Methods: A decision-analytic model was constructed to reflect one-year outcomes post-stroke, aligned with the stroke severity categories of the modified Rankin scale (mRS). Decision analysis compared outcomes following implementation of the QASC protocol versus no implementation. Population data were extracted from Australian databases and data inputs regarding stroke incidence, costs, and utilities were drawn from published sources. The analysis assumed a progressive uptake and efficacy of the QASC protocol over five years. Health benefits and costs were discounted by 5% annually. The cost of each year lived by an Australian, from a societal perspective, was based on the Australian Government's 'value of statistical life year' (AUD 213,000).

Results: Over five years, the model predicted 263,722 strokes among the Australian population. The implementation of the QASC protocol was predicted to prevent 1,154 deaths and yield a gain of 876 years of life (0.003 per stroke), and 3,180 quality-adjusted life years (QALYs) (0.012 per stroke). There was an estimated net saving of AUD 65.2 million in healthcare costs (AUD 247 per stroke) and AUD 251.7 million in societal costs (AUD 955 per stroke).

Conclusions: Implementation of the QASC protocol in Australia represents both a dominant (cost-saving) strategy, from a healthcare and a societal perspective.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105931DOI Listing
August 2021

Trends in the Utilization of Lipid-Lowering Medications in Australia: An Analysis of National Pharmacy Claims Data.

Curr Probl Cardiol 2021 May 8:100880. Epub 2021 May 8.

School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.

Lipid-lowering medications comprise standard of care in the prevention of cardiovascular disease. This study examined the trends in the utilization of statin and non-statin medications in the Australian general population between 2013 and 2019. Pharmacoepidemiological analyses were performed using pharmacy dispensing data from Australian Pharmaceutical Benefits Scheme. One-year prevalence and incidence of statin and non-statin prescribing patterns were reported, and relative variations in prescribing examined via Poisson regression modelling. The one-year prevalence of statins' prescriptions decreased between 2013-2019 by 5.5% (from 25.0%-19.5%). Females were less likely than males to be prescribed statins (rate ratio [RR]=0.90, 95% confidence interval [CI] 0.89-0.91). The one-year prevalence of ezetimibe alone, and in combination with statins, increased consistently from 2013-2019 from 1.5%-3.6% (P<0.01) and 0.1%-1.1% (P<0.01), respectively. The prevalence was higher among those aged 61-80 years (RR=1.20, 95%CI 1.10-1.21) and those aged older than 80 years (RR=1.34, 95%CI 1.22-1.47), when compared to people aged <60 years. The incidence of ezetimibe prescriptions was highest in people aged 61-80 years (RR=1.36, 95%CI 1.31-1.41) compared to those aged <60 years. The one-year prevalence of proprotein convertase subtilisin/kexin type 9 inhibitor prescriptions was highest among those aged 46-60 years (RR=1.24, 95%CI 0.97-4.97) compared to people aged <46 and >60 years. Females were less likely than males to be prescribed a proprotein convertase subtilisin/kexin type 9 inhibitor (RR=0.87, 95%CI 0.75-0.98). Statins remain the most prevalent lipid-lowering medication prescribed in Australia. The prescribing of non-statin medications remains low, but is increasing.
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http://dx.doi.org/10.1016/j.cpcardiol.2021.100880DOI Listing
May 2021

Switching, Persistence and Adherence to Statin Therapy: a Retrospective Cohort Study Using the Australian National Pharmacy Data.

Cardiovasc Drugs Ther 2021 Jun 7. Epub 2021 Jun 7.

School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Rd, Melbourne, 3004, Australia.

Background: Statins are widely prescribed for the primary and secondary prevention of cardiovascular disease (CVD), but their effectiveness is dependent on the level of adherence and persistence.

Objectives: This study aimed to explore the patterns of switching, adherence and persistence among the Australian general population with newly dispensed statins.

Methods: A retrospective cohort study was conducted using a random sample of data from the Australian national prescription claims data. Switching, adherence to and persistence with statins were assessed for people starting statins from 1 January 2015 to 31 December 2019. Switching was defined as either switching to another intensity of statin, to another statin or to a non-statin agent. Non-persistence to treatment was defined as discontinuation (i.e. ≥90 days with no statin) of coverage. Adherence was measured using proportion of days covered (PDC), and patients with PDC < 0.80 were considered non-adherent. Cox proportional hazard models were used to compare discontinuation, switching and reinitiation between different statins.

Results: A cohort of 141,062 people dispensed statins and followed over a median duration of 2.5 years were included. Of the cohort, 29.3% switched statin intensity, 28.4% switched statin type, 3.7% switched to ezetimibe and in 2.7%, ezetimibe was added as combination therapy during the study period. Overall, 58.8% discontinued statins based on the 90-day gap criteria, of whom 55.2% restarted. The proportion of people non-adherent was 24.0% at 6 months to 49.0% at 5 years. People on low and moderate intensity statins were more likely to discontinue compared to those on high-intensity statins (hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.09-1.31), (HR 1.28, 95%CI 1.14-1.42), respectively. Compared to maintaining same statin type and intensity, switching statins, which includes up-titration (HR 0.77, 95%CI 0.70 to 0.86) was associated with less likelihood of discontinuation after reinitiation.

Conclusions: Long-term persistence and adherence to statins remains generally poor among Australians, which limits the effectiveness of these medicines and the consequent health impact they may provide for individuals (and by extension, the population impact when poor persistence and adherence is considered in the statin-taking population). Switching between statins is prevalent in one third of statin users, although any clinical benefit of the observed switching trend is unknown. This, combined with the high volume of statin prescriptions, highlights the need for better strategies to address poor persistence and adherence.
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http://dx.doi.org/10.1007/s10557-021-07199-7DOI Listing
June 2021

Redundancy in meta-analyses publications-Time to pull the plug.

J Thromb Haemost 2021 06;19(6):1589-1590

Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic., Australia.

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http://dx.doi.org/10.1111/jth.15309DOI Listing
June 2021

Projecting the Incidence of Type 2 Diabetes-Related End-Stage Kidney Disease Until 2040: A Comparison Between the Effects of Diabetes Prevention and the Effects of Diabetes Treatment.

Diabetes Care 2021 May 23. Epub 2021 May 23.

Baker Heart and Diabetes Institute, Melbourne, Australia.

Objective: This study sought to examine the effects of two diabetes prevention approaches and of widespread use of sodium-glucose cotransporter 2 inhibitors (SGLT2is) among people with diabetes on the future incidence of diabetes-related end-stage kidney disease (ESKD-D).

Research Design And Methods: We developed a life table model to project the incidence of ESKD-D for type 2 diabetes in Australia until 2040. We projected incident ESKD-D under three separate scenarios: a large-scale lifestyle modification program for diabetes prevention; a population-wide sugar-sweetened beverage tax for diabetes prevention; and widespread use of SGLT2is among people with diabetes.

Results: Assuming current trends, we projected that the annual incidence of ESKD-D will increase from 3.7 per 100,000 of the general population in 2014 to 5.7 by 2040. Incorporating the diabetes prevention approaches, we projected that the annual incidence of ESKD-D will be between 5.2 and 5.5 per 100,000 by 2040. When we modeled scenarios in which 50% and 70% of eligible people with diabetes were prescribed an SGLT2i, the annual incidence of ESKD-D by 2040 was projected to be 4.7 and 4.3 per 100,000, respectively. SGLT2is were projected to reduce the total number of incident ESKD-D cases between 2020 and 2040 by 12-21% compared with current trends, whereas diabetes prevention reduced cases by 1-3%.

Conclusions: It is likely that the number of people developing ESKD-D will increase over the coming decades, although widespread SGLT2i use will be effective at limiting this increase. Diabetes prevention will be crucial to prevent an ever-increasing burden of diabetes complications.
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http://dx.doi.org/10.2337/dc21-0220DOI Listing
May 2021

Intravascular Ultrasound Versus Angiography-Guided Drug-Eluting Stent Implantation: A Health Economic Analysis.

Circ Cardiovasc Qual Outcomes 2021 May 18;14(5):e006789. Epub 2021 May 18.

The Alfred Hospital, Melbourne, Australia (J.Z., D.L., S.J.D., J.S., A.W., W.C., D.S.).

Background: There is increasing evidence that use of intravascular ultrasound (IVUS) guidance during percutaneous coronary intervention (PCI) is associated with improved clinical outcomes compared with angiography guidance alone. However, concern regarding the cost-effectiveness of IVUS has limited use of this technology worldwide. In this study, we aimed to evaluate the cost-effectiveness of IVUS-guided PCI compared with angiography-guided PCI in patients undergoing drug-eluting stent implantation.

Methods: A decision-analytic Markov model was constructed to compare the cost-effectiveness of IVUS to angiography guidance from the Australian healthcare system perspective. Procedure-related morbidity and mortality were estimated from the literature. Costs were obtained from Australian sources. The population of interest was all-comers undergoing PCI with drug-eluting stent. Outcomes of interest included costs, life-expectancy, and quality-adjusted life years (QALYs) for both treatment groups.

Results: In the base case, IVUS guidance was cost-effective compared with angiography guidance alone. With 5% annual discounting, IVUS was associated with increased lifetime costs of Australian dollars (AUD) $823 (USD $597) per person and benefits of 0.04 life years and 0.05 QALYs compared with angiography, yielding an incremental cost-effectiveness ratio of AUD $17 539 (USD $12 730) per QALY gained. Results were robust to sensitivity analyses, with IVUS being cost-effective in 99% of 10 000 Monte Carlo iterations assuming a willingness-to-pay threshold of AUD $50 000 per QALY gained. In a worst-case scenario analysis, IVUS remained the cost-effective option, with an ICER of AUD $36 651 (USD $26 601) per QALY gained. Exploratory subgroup analysis revealed that cost-effectiveness may be greatest among patients with left main and complex coronary lesions.

Conclusions: Use of IVUS guidance during PCI is likely to be cost-effective compared with angiography guidance alone among patients undergoing drug-eluting stent implantation.
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http://dx.doi.org/10.1161/CIRCOUTCOMES.120.006789DOI Listing
May 2021

First-line Treatment with Empagliflozin and Metformin Combination Versus Standard Care for Patients with Type 2 Diabetes Mellitus and Cardiovascular Disease in Qatar. A Cost-Effectiveness Analysis.

Curr Probl Cardiol 2021 Apr 6:100852. Epub 2021 Apr 6.

School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. Electronic address:

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown to reduce cardiovascular events and mortality in patients with type 2 diabetes mellitus (T2DM), but they are currently not used as first-line therapy in clinical practice. This study sought to evaluate the cost-effectiveness of first-line empagliflozin plus standard care for patients with newly diagnosed T2DM and existing cardiovascular disease (CVD). A decision-analytic Markov model with one-year cycles and a lifetime time horizon was developed from the perspective of the Qatari healthcare system to compare first-line empagliflozin combined with metformin versus metformin monotherapy for patients aged 50 to 79 years with T2DM and existing CVD. Two health states were considered: 'Alive with CVD and T2DM' and 'Dead'. Patients could experience non-fatal myocardial infarction, non-fatal stroke, hospitalization for heart failure, hospitalization for unstable angina, and cardiovascular or non-cardiovascular death. Model inputs were ascertained from published and publicly available sources in Qatar. Costs and outcomes were discounted at 3% per annum. Sensitivity analyses were conducted to evaluate parameter uncertainty. The model predicted that adding empagliflozin to current standard care led to additional 1.9 years of life saved (YoLS) and 1.5 quality-adjusted life year (QALYs) per person, and an incremental cost of QAR 56,869 (USD 15,619), which equated to an incremental cost-effectiveness ratio of QAR 30,675 (USD 8,425) per YoLS and QAR 39,245 (USD 10,779) per QALY. Sensitivity analyses showed the findings to be robust. First-line empagliflozin combined with metformin appears to be a cost-effective therapeutic option for patients with T2DM and CVD.
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http://dx.doi.org/10.1016/j.cpcardiol.2021.100852DOI Listing
April 2021

Estimating the Productivity Impact of Acute Myeloid Leukemia in Australia Between 2020 and 2029, Using a Novel Work Utility Measure: The Productivity-Adjusted Life Year (PALY).

JCO Oncol Pract 2021 May 12:OP2000904. Epub 2021 May 12.

Monash University, School of Public Health and Preventive Medicine, Melbourne, Australia.

Purpose: Acute myeloid leukemia (AML) is a rare hematologic malignancy accounting for 0.8% of new cancer diagnoses in Australia. High mortality and morbidity affect work productivity through workforce dropout and premature death. This study sought to estimate the productivity loss attributable to AML in the Australian population over 10 years and to estimate the costs of this productivity loss. Productivity was measured using productivity-adjusted life years (PALYs), a similar concept to quality-adjusted life years, but adjusts for the productivity loss attributable to disease, rather than impaired health.

Materials And Methods: Dynamic life tables modeled the Australian working population (age 15-65 years) between 2020 and 2029. The model population had two cohorts: those with and without AML. Differences in life years, PALYs, and costs represented the health and productivity impact of AML. Secondary analyses evaluated the impact of different scenarios.

Results: Over the next 10 years, there will be 7,600 years of life lost and 7,337 PALYs lost because of AML, amounting to Australian dollars (AU$) 1.43 billion in lost gross domestic product ($971 million in US dollars). Secondary analyses highlight potential savings of approximately AU$52 million if survival rates were improved by 20% and almost AU$118 million in savings if the return-to-work rates increased by 20% on the current estimates.

Conclusion: Our study demonstrates that even in low-incidence cancer, high mortality and morbidity translate to profound impacts on years of life, productivity, and the broader economy. Better treatment strategies are likely to result in significant economic gains. This highlights the value of investing in research for improved therapies.
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http://dx.doi.org/10.1200/OP.20.00904DOI Listing
May 2021

Impact of emergency medical service delays on time to reperfusion and mortality in STEMI.

Open Heart 2021 May;8(1)

School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia

Objectives: To explore the relationship between emergency medical service (EMS) delay time, overall time to reperfusion and clinical outcome in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI).

Methods: This was a retrospective observational study of 2976 patients with STEMI who presented to EMS and underwent PPCI between January 2014 and December 2017. We performed multivariable logistic models to assess the relationship between EMS delay time and 30-day mortality and to identify factors associated with system delay time.

Results: EMS delay time accounted for the first half of total system delay (median=59 min (IQR=48-77)). Compared with those who survived, those who died had longer median EMS delay times (59 (IQR=11-74) vs 74 (IQR=57-98), p<0.001). EMS delay time was independently associated with a higher risk of mortality (adjusted OR 1.20; 95% CI 1.02 to 1.40, for every 30 min increase), largely driven by complicated patients with cardiogenic shock or cardiac arrest. Independent predictors of longer EMS delay times were older age, women, cardiogenic shock, cardiac arrest, prehospital notification and intensive care management. Although longer EMS delay times were associated with shorter door-to-balloon times, total system delay times increased with increasing EMS delay times.

Conclusion: Increasing EMS delay times, particularly those result from haemodynamic complications, increase total time to reperfusion and are associated with 30-day mortality after STEMI. All efforts should be made to monitor and reduce EMS delay times for timely reperfusion and better outcome.
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http://dx.doi.org/10.1136/openhrt-2021-001654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108686PMC
May 2021

National Heart Foundation of Australia: position statement on coronary artery calcium scoring for the primary prevention of cardiovascular disease in Australia.

Med J Aust 2021 05 7;214(9):434-439. Epub 2021 May 7.

National Heart Foundation of Australia, Melbourne, VIC.

Introduction: This position statement considers the evolving evidence on the use of coronary artery calcium scoring (CAC) for defining cardiovascular risk in the context of Australian practice and provides advice to health professionals regarding the use of CAC scoring in primary prevention of cardiovascular disease in Australia. Main recommendations: CAC scoring could be considered for selected people with moderate absolute cardiovascular risk, as assessed by the National Vascular Disease Prevention Alliance (NVDPA) absolute cardiovascular risk algorithm, and for whom the findings are likely to influence the intensity of risk management. (GRADE evidence certainty: Low. GRADE recommendation strength: Conditional.) CAC scoring could be considered for selected people with low absolute cardiovascular risk, as assessed by the NVDPA absolute cardiovascular risk algorithm, and who have additional risk-enhancing factors that may result in the underestimation of risk. (GRADE evidence certainty: Low. GRADE recommendation strength: Conditional.) If CAC scoring is undertaken, a CAC score of 0 AU could reclassify a person to a low absolute cardiovascular risk status, with subsequent management to be informed by patient-clinician discussion and follow contemporary recommendations for low absolute cardiovascular risk. (GRADE evidence certainty: Very low. GRADE recommendation strength: Conditional.) If CAC scoring is undertaken, a CAC score > 99 AU or ≥ 75th percentile for age and sex could reclassify a person to a high absolute cardiovascular risk status, with subsequent management to be informed by patient-clinician discussion and follow contemporary recommendations for high absolute cardiovascular risk. (GRADE evidence certainty: Very low. GRADE recommendation strength: Conditional.) CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: CAC scoring can have a role in reclassification of absolute cardiovascular risk for selected patients in Australia, in conjunction with traditional absolute risk assessment and as part of a shared decision-making approach that considers the preferences and values of individual patients.
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http://dx.doi.org/10.5694/mja2.51039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252756PMC
May 2021

Characterising experiences with acute myeloid leukaemia using an Instagram content analysis.

PLoS One 2021 3;16(5):e0250641. Epub 2021 May 3.

School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.

Instagram has more than one billion monthly users, which presents a unique research opportunity particularly in rare diseases or hard to reach populations. This study focuses on acute myeloid leukaemia, a rare haematological malignancy and aims to characterise who posts acute myeloid leukaemia-related content and the type of content created. The findings can provide information and a method for future studies, particularly those focused on online or social media based interventions. Acute myeloid leukaemia-related Instagram posts were identified by searching specific and relevant hashtags (#). A content analysis systematically classified themes in the data. A convenience sample of 100 posts (138 photos) were manually extracted and coded. Data are described using descriptive statistics and demonstrated by qualitative examples. The most frequent users in our sample were patients (66%), patient support networks (24%) and professional organisations (10%). Patients who were communicating their health update (31%) were the most frequently posted content and 25% of these posts described a symptom experience. Our findings demonstrate that patients and their support networks are frequenting Instagram and therefore may be able to receive and benefit from tailored intervention, however there is an identified gap in health-organisations participating in this virtual online community.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250641PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092772PMC
May 2021

Kidney age - chronological age difference (KCD) score provides an age-adapted measure of kidney function.

BMC Nephrol 2021 Apr 26;22(1):152. Epub 2021 Apr 26.

University of Melbourne, Parkville, Victoria, Australia.

Background: Given the age-related decline in glomerular filtration rate (GFR) in healthy individuals, we examined the association of all-cause death or cardiovascular event with the Kidney age - Chronological age Difference (KCD) score, whereby an individual's kidney age is estimated from their estimated GFR (eGFR) and the age-dependent eGFR decline reported for healthy living potential kidney donors.

Methods: We examined the association between death or cardiovascular event and KCD score, age-dependent stepped eGFR criteria (eGFRstep), and eGFR < 60 ml/min/1.73 m (eGFR60) in a community-based high cardiovascular risk cohort of 3837 individuals aged ≥60 (median 70, interquartile range 65, 75) years, followed for a median of 5.6 years.

Results: In proportional hazards analysis, KCD score ≥ 20 years (KCD20) was associated with increased risk of death or cardiovascular event in unadjusted analysis and after adjustment for age, sex and cardiovascular risk factors. Addition of KCD20, eGFRstep or eGFR60 to a cardiovascular risk factor model did not improve area under the curve for identification of individuals who experienced death or cardiovascular event in receiver operating characteristic curve analysis. However, addition of KCD20 or eGFR60, but not eGFRstep, to a cardiovascular risk factor model improved net reclassification and integrated discrimination. KCD20 identified individuals who experienced death or cardiovascular event with greater sensitivity than eGFRstep for all participants, and with greater sensitivity than eGFR60 for participants aged 60-69 years, with similar sensitivities for men and women.

Conclusions: In this high cardiovascular risk cohort aged ≥60 years, the KCD score provided an age-adapted measure of kidney function that may assist patient education, and KCD20 provided an age-adapted criterion of eGFR-related increased risk of death or cardiovascular event. Further studies that include the full age spectrum are required to examine the optimal KCD score cut point that identifies increased risk of death or cardiovascular event, and kidney events, associated with impaired kidney function, and whether the optimal KCD score cut point is similar for men and women.

Trial Registration: ClinicalTrials.gov NCT00400257 , NCT00604006 , and NCT01581827 .
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http://dx.doi.org/10.1186/s12882-021-02324-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077774PMC
April 2021

An open-label, non-inferiority randomized controlled trial of lidocAine Versus Opioids In MyocarDial Infarction study (AVOID-2 study) methods paper.

Contemp Clin Trials 2021 Jun 22;105:106411. Epub 2021 Apr 22.

Department of Cardiology, Alfred Hospital, Melbourne, Australia; Baker Heart and Diabetes Institute, Melbourne, Australia; Monash University, Melbourne, Australia; Department of Cardiology, Western Health, Melbourne, Australia. Electronic address:

Background There is increasing evidence that opioids interfere with the oral bioavailability of P2Y inhibitors leading to delayed onset of antiplatelet effects. Several strategies have been proposed to mitigate this interaction including utilizing alternative analgesic agents in the management of ischemic chest pain. Methods The lidocAine Versus Opioids In MyocarDial Infarction (AVOID-2) study is a phase II, pre-hospital, open-label, non-inferiority, randomized controlled trial conducted by Ambulance Victoria and Monash University in metropolitan Melbourne, Victoria, Australia. The purpose of the study is to compare the analgesic effect (reduction in pain by arrival to hospital) and safety (e.g. adverse drug reactions) (co-primary endpoints) of intravenous lidocaine versus intravenous fentanyl in 300 adult patients attended by ambulance with suspected ST-elevation myocardial infarction (STEMI). Secondary endpoints and a cardiac magnetic resonance imaging (MRI) sub-study will also compare infarct size between these two groups. Conclusions The evaluation of alternative analgesic agents in the management of acute coronary syndromes is urgently needed to manage the opioid-P2Y inhibitor interaction. The results of this trial will have significant implications on the emergency management of acute coronary syndromes internationally.
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http://dx.doi.org/10.1016/j.cct.2021.106411DOI Listing
June 2021

Comparison of EQ-5D-3L with QLU-C10D in Metastatic Melanoma Using Cost-Utility Analysis.

Pharmacoecon Open 2021 Apr 23. Epub 2021 Apr 23.

School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, 3004, Australia.

Background: The National Institute for Health and Care Excellence (NICE) prefers the use of the generic EQ-5D instrument to estimate quality-adjusted life years (QALYs), and recommends that condition-specific instruments only be used when EQ-5D data are not available or not appropriate.

Objective: This study aimed to compare the utility gain and cost-effectiveness results of using the generic EQ-5D-3L instrument to the condition-specific Quality-of-Life Utility Measure-Core 10 dimensions (QLU-C10D) by applying both sets of values in a published cost-utility analysis (CUA) of immunotherapy for metastatic melanoma.

Methods: Quality-of-life data were drawn from a clinical study in which both QLQ-C30 and EQ-5D-3L tools were used. The potential influence of the two instruments on cost-effectiveness was assessed using a three-state Markov model. Descriptive statistics and standard health economic outputs were compared between analyses that applied the two different utility measures.

Results: Mean baseline utility values as measured by the QLU-C10D (mean = 0.744, SD = 0.219) were not statistically different (p > 0.05) compared to values derived from EQ-5D-3L (mean = 0.735, SD = 0.239). The two instruments were correlated (Pearson's correlation = 0.74); however, concordance was low (Lin's concordance correlation coefficient < 0.90) at baseline. The model predicted slightly higher QALYs gained when using EQ-5D-3L over QLU-C10D-derived utilities (1.87 vs 1.74, respectively). This resulted in an incremental cost-effectiveness ratio of US$30.5K when using EQ-5D-3L utilities, compared to US$32.7K when using QLU-C10D utilities. Cost-effectiveness acceptability curves based on the two sets of utilities were almost indistinguishable.

Conclusion: This study supports the use of the generic EQ-5D instrument in immunotherapy treated metastatic melanoma, and found no additional benefit for using the disease-specific QLU-C10D when using Australian weights.
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http://dx.doi.org/10.1007/s41669-021-00265-8DOI Listing
April 2021

Cost-analysis of opportunistic influenza vaccination in general medical inpatients.

Intern Med J 2021 Apr;51(4):591-595

School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.

Influenza vaccination is an important preventative health measure in the elderly and those with medical comorbidities. It has been shown to reduce hospitalisations, cardiovascular and respiratory complications. A significant proportion of patients admitted to general medicine are eligible for opportunistic inpatient influenza vaccination. This study explores the cost-effectiveness of such a strategy in reducing subsequent healthcare utilisation costs.
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http://dx.doi.org/10.1111/imj.15270DOI Listing
April 2021

Applying a framework to assess the impact of cardiovascular outcomes improvement research.

Health Res Policy Syst 2021 Apr 21;19(1):67. Epub 2021 Apr 21.

Department of Epidemiology and Preventative Medicine, Monash University, Melbourne, Australia.

Background: Health and medical research funding agencies are increasingly interested in measuring the impact of funded research. We present a research impact case study for the first four years of an Australian National Health and Medical Research Council funded Centre of Research Excellence in Cardiovascular Outcomes Improvement (2016-2020). The primary aim of this paper was to explore the application of a research impact matrix to assess the impact of cardiovascular outcomes improvement research.

Methods: We applied a research impact matrix developed from a systematic review of existing methodological frameworks used to measure research impact. This impact matrix was used as a bespoke tool to identify and understand various research impacts over different time frames. Data sources included a review of existing internal documentation from the research centre and publicly available information sources, informal iterative discussions with 10 centre investigators, and confirmation of information from centre grant and scholarship recipients.

Results: By July 2019, the impact on the short-term research domain category included over 41 direct publications, which were cited over 87 times (median journal impact factor of 2.84). There were over 61 conference presentations, seven PhD candidacies, five new academic collaborations, and six new database linkages conducted. The impact on the mid-term research domain category involved contributions towards the development of a national cardiac registry, cardiovascular guidelines, application for a Medicare Benefits Schedule reimbursement item number, introduction of patient-reported outcome measures into several databases, and the establishment of nine new industry collaborations. Evidence of long-term impacts were described as the development and use of contemporary management for aortic stenosis, a cardiovascular risk prediction model and prevention targets in several data registries, and the establishment of cost-effectiveness for stenting compared to surgery.

Conclusions: We considered the research impact matrix a feasible tool to identify evidence of academic and policy impact in the short- to midterm; however, we experienced challenges in capturing long-term impacts. Cost containment and broader economic impacts represented another difficult area of impact to measure.
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http://dx.doi.org/10.1186/s12961-021-00710-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059028PMC
April 2021

The economic impact of sudden cardiac arrest.

Resuscitation 2021 Apr 15;163:49-56. Epub 2021 Apr 15.

Baker Heart and Diabetes Institute, 75 Commercial Rd, Prahran, VIC, 3181, Australia; Alfred Hospital, 55 Commercial Rd, Prahran, VIC, 3181, Australia; St Vincent's Hospital Melbourne, 41 Victoria Pde, Fitzroy, VIC, 3065, Australia.

Background: There are 20,000 sudden cardiac arrests (SCAs) in Australia annually, with 90% case-fatality.

Objective: The present study calculated both the health and economic impact of SCAs in Victoria, Australia.

Methods: Data on all SCAs attended by Ambulance Victoria from July 2017 to June 2018 were collected regarding age, gender, and survival to hospital, discharge and 12 months. Pre-SCA employment status of all patients was modelled using age and gender-matched Australian economic data. A Markov state-transition model with a five-year horizon calculated health and economic impact in years of life lived (YLL), productivity-adjusted life years (PALYs) and gross domestic product (GDP) lost. A counterfactual Markov state-transition model assessed outcomes of an identical cohort of patients who did not experience SCA. All values were discounted by 5%.

Results: In 12 months, 4637 people suffered SCAs in Victoria, of whom 1516 (32.7%) were working at the time. 695 patients (15.0%) survived to hospital, 325 (7.0%) to discharge, and 303 (6.5%) to 12 months. In five years following their SCA, the cohort lost 15,922 years of life and 2327 PALYs. Reduced productivity led to GDP losses of AUD$448 million (92.8% relative reduction). Extrapolated to the 20,000 SCAs occurring across all of Australia, total GDP losses approached AUD$2 billion.

Conclusion: The health and economic burden of SCAs is high, predominantly underpinned by very high mortality. Annual national losses approach AUD$2 billion (USD$1.42 billion) and are comparable to productivity losses from all cancers combined. Prioritising research and state-of-the-art care for SCA patients appears economically sound.
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http://dx.doi.org/10.1016/j.resuscitation.2021.04.001DOI Listing
April 2021

The Preventable Productivity Burden of Kidney Disease in Australia.

J Am Soc Nephrol 2021 Mar 9. Epub 2021 Mar 9.

School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia

Background: Kidney disease is associated with impaired work productivity. However, the collective effect of missed work days, reduced output at work, and early withdrawal from the workforce is rarely considered in health-economic evaluations.

Methods: To determine the effect on work productivity of preventing incident cases of kidney disease, using the novel measure "productivity-adjusted life year" (PALY), we constructed a dynamic life table model for the Australian working-age population (aged 15-69 years) over 10 years (2020-2029), stratified by kidney-disease status. Input data, including productivity estimates, were sourced from the literature. We ascribed a financial value to the PALY metric in terms of gross domestic product (GDP) per equivalent full-time worker and assessed the total number of years lived, total PALYs, and broader economic costs (GDP per PALY). We repeated the model simulation, assuming a reduced kidney-disease incidence; the differences reflected the effects of preventing new kidney-disease cases. Outcomes were discounted by 5% annually.

Results: Our projections indicate that, from 2020 to 2029, the estimated number of new kidney-disease cases will exceed 161,000. Preventing 10% of new cases of kidney disease during this period would result in >300 premature deaths averted and approximately 550 years of life and 7600 PALYs saved-equivalent to a savings of US$1.1 billion in GDP or US$67,000 per new case avoided.

Conclusions: Pursuing a relatively modest target for preventing kidney disease in Australia may prolong years of life lived and increase productive life years, resulting in substantial economic benefit. Our findings highlight the need for investment in preventive measures to reduce future cases of kidney disease.
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http://dx.doi.org/10.1681/ASN.2020081148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017534PMC
March 2021

Future burden of cardiovascular disease in Australia: impact on health and economic outcomes between 2020 and 2029.

Eur J Prev Cardiol 2021 Mar 4. Epub 2021 Mar 4.

School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Rd, Melbourne 3004, Australia.

Aims: To estimate the health and economic burden of new and established cardiovascular disease from 2020 to 2029 in Australia.

Methods And Results: A two-stage multistate dynamic model was developed to predict the burden of the incident and prevalent cardiovascular disease, for Australians 40-90 years old from 2020 to 2029. The model captured morbidity, mortality, years of life lived, quality-adjusted life years, healthcare costs, and productivity losses. Cardiovascular risk for the primary prevention population was derived using Australian demographic data and the Pooled Cohort Equation. Risk for the secondary prevention population was derived from the REACH registry. Input data for costs and utilities were extracted from published sources. All outcomes were annually discounted by 5%. A number of sensitivity analyses were undertaken to test the robustness of the study. Between 2020 and 2029, the model estimates 377 754 fatal and 991 375 non-fatal cardiovascular events. By 2029, 1 061 756 Australians will have prevalent cardiovascular disease (CVD). The population accrued 8 815 271 [95% uncertainty interval (UI) 8 805 083-8 841 432] years of life lived with CVD and 5 876 975 (5 551 484-6 226 045) QALYs. The total healthcare costs of CVD were projected to exceed Australian dollars (AUD) 61.89 (61.79-88.66) billion, and productivity losses will account for AUD 78.75 (49.40-295.25) billion, driving the total cost to surpass AUD 140.65 (123.13-370.23) billion.

Conclusion: Cardiovascular disease in Australia has substantial impacts in terms of morbidity, mortality, and lost revenue to the healthcare system and the society. Our modelling provides important information for decision making in relation to the future burden of cardiovascular disease.
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http://dx.doi.org/10.1093/eurjpc/zwab001DOI Listing
March 2021

Association of Spicy Chilli Food Consumption With Cardiovascular and All-Cause Mortality: A Meta-Analysis of Prospective Cohort Studies.

Angiology 2021 08 4;72(7):625-632. Epub 2021 Mar 4.

Department of Twin Research and Genetic Epidemiology, 4616Kings College London, London, UK.

This systematic review and meta-analysis examined the association between spicy food (chilli pepper, chilli sauce, or chilli oil) consumption with cardiovascular and all-cause mortality. Medline and EMBASE were searched from their inception until February 2020 to identify relevant prospective cohort studies. Hazard ratios (HRs)/relative risk (RRs) were pooled via random-effect meta-analysis. Of the 4387 citations identified, 4 studies (from the United States, China, Italy, and Iran) were included in the meta-analysis. The included studies involved a total of 564 748 adults (aged ≥18 years; 51.2% female) followed over a median duration of 9.7 years. The pooled data suggested that compared with people who did not regularly consume spicy food (none/<1 d/wk), regular consumers of spicy food experienced a 12% (HR/RR 0.88, 95% CI, 0.86-0.90; = 0%) lower risk of all-cause mortality. Moreover, spicy food consumption was associated with significant reduction in the risk of death from cardiac diseases (HR/RR 0.82, 0.73-0.91; = 0%), but not from cerebrovascular disorders (HR/RR 0.79, 0.53-1.17; = 72.2%). In conclusion, available epidemiological studies suggest that the consumption of spicy chilli food is associated with reduced risk of all-cause as well as heart disease-related mortality. Further studies in different populations are needed to confirm this association.
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http://dx.doi.org/10.1177/0003319721995666DOI Listing
August 2021

Aetiologies and factors associated with poor clinical outcomes in rhabdomyolysis: a retrospective cohort study in an Australian trauma centre.

Intern Med J 2021 Feb;51(2):264-267

Department of General Medicine, The Alfred Hospital, Melbourne, Victoria, Australia.

Rhabdomyolysis is a clinical syndrome with significant morbidity and mortality that occurs as a result of traumatic and non-traumatic aetiologies. Acute kidney injury, the need for dialysis, and death, can occur due to rhabdomyolysis. This study explores the aetiologies, clinical outcomes and associated factors for poor outcomes in a cohort of patients with rhabdomyolysis in a tertiary trauma centre in Australia.
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http://dx.doi.org/10.1111/imj.15183DOI Listing
February 2021

The impact of coronary heart disease prevention on work productivity: a 10-year analysis.

Eur J Prev Cardiol 2021 May;28(4):418-425

School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Rd, Melbourne, VIC 3004, Australia.

Aims: To determine the impact of preventing new (incident) cases of coronary heart disease (CHD) on years of life and productivity, using the novel measure 'productivity-adjusted life year' (PALY), over the next 10 years.

Methods And Results: A dynamic life table model was constructed for the total Australian working-age population (15-69 years) over 10 years (2020-2029), separated by CHD status. Productivity estimates were sourced from the literature. The PALY was ascribed a financial value in terms of gross domestic product (GDP) per equivalent full-time worker. The total number of years lived, PALYs, and economic burden (in terms of GDP per PALY) were estimated. The model simulation was repeated assuming incidence was reduced, and the differences represented the impact of CHD prevention. All outcomes were discounted by 5% per annum. Over 10 years, the total projected years lived and PALYs in the Australian working-age population (with and without CHD) were 133 million and 83 million, respectively, amounting to A$17.2 trillion in GDP. We predicted more than 290 000 new (incident) CHD cases over the next 10 years. If all new cases of CHD could be prevented during this period, a total of 4 000 deaths could be averted, resulting in more than 8 000 years of life saved and 104 000 PALYs gained, equivalent to a gain of nearly A$21.8 billion (US$14.8 billion) in GDP.

Conclusion: Prevention of CHD will prolong years of life lived and productive life years, resulting in substantial economic benefit. Policy makers and employers are encouraged to engage in preventive measures addressing CHD.
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http://dx.doi.org/10.1093/eurjpc/zwaa037DOI Listing
May 2021

Attenuating PI3K/Akt- mTOR pathway reduces dihydrosphingosine 1 phosphate mediated collagen synthesis and hypertrophy in primary cardiac cells.

Int J Biochem Cell Biol 2021 May 17;134:105952. Epub 2021 Feb 17.

Biomarker Discovery Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia; Monash Centre of Cardiovascular Research and Education in Therapeutics, Melbourne, Australia. Electronic address:

Cardiac fibrosis and myocyte hypertrophy play contributory roles in the progression of diseases such as heart Failure (HF) through what is collectively termed cardiac remodelling. The phosphoinositide 3- kinase (PI3K), protein kinase B (Akt) and mammalian target for rapamycin (mTOR) signalling pathway (PI3K/Akt- mTOR) is an important pathway in protein synthesis, cell growth, cell proliferation, and lipid metabolism. The sphingolipid, dihydrosphingosine 1 phosphate (dhS1P) has been shown to bind to high density lipids in plasma. Unlike its analog, spingosine 1 phosphate (S1P), the role of dhS1P in cardiac fibrosis is still being deciphered. This study was conducted to investigate the effect of dhS1P on PI3K/Akt signalling in primary cardiac fibroblasts and myocytes. Our findings demonstrate that inhibiting PI3K reduced collagen synthesis in neonatal cardiac fibroblasts (NCFs), and hypertrophy in neonatal cardiac myocytes (NCMs) induced by dhS1P, in vitro. Reduced activation of the PI3K/Akt- mTOR signalling pathway led to impaired translation of fibrotic proteins such as collagen 1 (Coll1) and transforming growth factor β (TGFβ) and inhibited the transcription and translation of tissue inhibitor of matrix metalloproteinase 1 (TIMP1). PI3K inhibition also affected the gene expression of S1P receptors and enzymes such as the dihydroceramide delta 4 desaturase (DEGS1) and sphingosine kinase 1 (SK1) in the de novo sphingolipid pathway. While in myocytes, PI3K inhibition reduced myocyte hypertrophy induced by dhS1P by reducing skeletal muscle α- actin (αSKA) mRNA expression, and protein translation due to increased glycogen synthase kinase 3β (GSK3β) mRNA expression. Our findings show a relationship between the PI3K/Akt- mTOR signalling cascade and exogenous dhS1P induced collagen synthesis and myocyte hypertrophy in primary neonatal cardiac cells.
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http://dx.doi.org/10.1016/j.biocel.2021.105952DOI Listing
May 2021